ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6487A>C (p.Lys2163Gln)

gnomAD frequency: 0.00002  dbSNP: rs759728732
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000775341 SCV000909613 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779713 SCV000916468 uncertain significance not specified 2018-04-13 criteria provided, single submitter clinical testing Variant summary: APC c.6487A>C (p.Lys2163Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 245562 control chromosomes and is found exclusively in the East Asian subpopulation with MAF of 0.0003480 (6/17242 chr). This frequency is about 5 fold higher than expected for a pathogenic variant in APC causing Familial Adenomatous Polyposis (2.4e-05 vs 7.1e-05), suggesting this variant is possibly a benign polymorphism primarily found in East Asians. c.6487A>C has been reported in the literature in in a Korean gastric cancer patient with co-occurrence of somatic APC variant c.1273delG, and authors classified variant of interest as benign (Kim_2017). However, this report does not provide unequivocal conclusions about an association of the variant with Familial Adenomatous Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly beingn.
Invitae RCV002535529 SCV001217969 uncertain significance Familial adenomatous polyposis 1 2023-12-08 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2163 of the APC protein (p.Lys2163Gln). This variant is present in population databases (rs759728732, gnomAD 0.03%). This missense change has been observed in individual(s) with gastric cancer (PMID: 29050249). This variant is also known as p.K2145Q. ClinVar contains an entry for this variant (Variation ID: 630197). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284248 SCV001469927 uncertain significance not provided 2020-01-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000775341 SCV002658124 benign Hereditary cancer-predisposing syndrome 2021-10-28 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.